PXD081798-1

PXD081798 is an original dataset announced via ProteomeXchange.

Title	PUM3 is an essential suppressor of replication stress in homologous recombination deficient breast cancer
Description	Most Triple Negative Breast Cancers (TNBCs) are p53 mutant high-grade invasive ductal carcinomas with a basal-like transcriptional programme. A large proportion of TNBCs also have mutation signatures indicating defective homologous recombination (HR) DNA repair. While HR deficiency is mutagenic and oncogenic, it can also compromise cell fitness. Here, we show that BLBCs harboring the recurrent 9p21.3–9p24 amplicon, and particularly those that are HR-defective, overexpress PUM3 (Pumilio RNA binding family member 3). PUM3 inhibition is also synthetic lethal in tumour cells that overexpress PUM3 including those that have BRCA1/BRCA2 defects. Mechanistically, PUM3 suppresses transcription-mediated replicative stress and R-loop accumulation, thereby preventing DNA damage that would normally require RAD51-mediated repair. Transcription/replication collisions are commonly resolved by topoisomerase TOP1; without PUM3, TOP1 DNA chromatin localisation is impaired, revealing one mechanism by which PUM3 limits replication stress. PUM3 is therefore required for the continued fitness of a BLBC subset, allowing tolerance of HR deficiency’s deleterious effects.
HostingRepository	PRIDE
AnnounceDate	2026-07-29
AnnouncementXML	Submission_2026-07-29_05:02:18.199.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-28 10:39:57	ID requested
⏵ 1	2026-07-29 05:02:18	announced

Dataset with its publication pending

submitter keyword: homologous recombination deficient breast cancer,PUM3

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD081798
     1. Label: PRIDE project
     2. Name: PUM3 is an essential suppressor of replication stress in homologous recombination deficient breast cancer